BIRTH DEFECT RISK FACTOR SERIES: Gastroschisis

Introduction

Definition

Gastroschisis is an abdominal wall defect located on either side of the umbilicus. No membranes cover the viscera, thus the organs develop outside the body and float in the amniotic fluid [1]. This defect is different from omphalocele, in which the abdominal organs are herniated into the base of the umbilicus, and are covered by a sac or even skin [2]. Infants with gastroschisis tend to have fewer additional birth defects than those with omphalocele, including chromosomal abnormalities [3], and a higher survival rate [4-14].

Prevalence

Birth prevalence in Texas among 1999-2008 deliveries was 4.82 cases per 10,000 live births [15]. Birth prevalence in the United States is 3.73 per 10,000 live births [16].

About half of Texas gastroschisis cases are prenatally diagnosed [17]. Prenatal diagnosis followed by terminations of affected pregnancies can lead to differences in reported rates among different surveillance systems [4, 7, 8, 16].

DEMOGRAPHIC AND REPRODUCTIVE FACTORS

Trends

Secular trends have been observed in gastroschisis prevalence since the 1970s. Overall, gastroschisis rates have increased over time in several regions around the world [1, 5, 6, 10, 18-33], although this trend has not always been noted [11, 13, 14, 34-36]. At least for some studies examining earlier periods, this trend may be due to misclassification of gastroschisis as other abdominal wall defects; however, for research examining later time periods, this is less likely to have been a plausible explanation for the prevalence increase.

Ethnicity

Several studies have investigated the relationship between ethnicity and risk for gastroschisis but failed to find any effect [10, 34, 37]. However, recent examinations have consistently found that African Americans have the lowest risk for gastroschisis when compared to other ethnic groups [16, 21, 22, 32, 36, 38-42]. Some research suggests that Hispanics have the highest risk of gastroschisis [16, 38, 43, 44], while others report that white infants are at greatest risk [40, 41]. Studies have suggested that foreign born mothers have a decreased risk when compared to mothers born in the United States [32, 41]. Other ethnic variations have been noted [1, 43, 45, 46]. There have also been differences reported in the survival rate for infants with gastroschisis. White infants with this defect are more likely to survive than black infants [47], but there are no clear reasons for this difference.

Parental Age

The most consistent finding among gastroschisis studies is the association between gastroschisis and younger maternal age [1, 5, 7, 9, 10, 13, 18, 20, 22, 24-27, 30-36, 38-41, 43-45, 48-56]. Research has also found a link between young paternal age and gastroschisis risk, independent of maternal age [22, 32, 54]. Further, a combination of both advanced maternal and older paternal age has shown to decrease the risk of gastroschisis [57].

Since gastroschisis risk is significantly increased with young maternal age, a number of studies have investigated factors that may be associated with younger mothers. Several studies reported that demographic variables indicating low maternal socioeconomic status were associated with increased rates of gastroschisis [23, 24, 37, 39-41, 43, 44, 46]. These variables included lower levels of maternal education and lower family income. Another investigation failed to find an association between education and gastroschisis risk [50] and one found no link between maternal and paternal education and gastroschisis risk [32]. Single marital status has also been linked to higher gastroschisis risk [23, 24, 41].

Geographic Location

Prevalence of gastroschisis displays variation by geographic location, both within and between countries [6, 10, 20, 21, 23, 25-33, 35, 36, 58]. Some research indicates that gastroschisis is more likely to occur in rural areas than urban ones [1, 21, 33]. Others have failed to find an association between maternal residence in rural areas and the risk of gastroschisis [21, 22].

Parity

A decline in gastroschisis risk with increasing parity has been identified [21, 24, 26, 31, 32, 39-41, 43, 44, 59, 60], but other examinations found no such relationship [10, 37]. An association between gastroschisis risk and a short interval between menarche and first pregnancy has been reported [37, 59], as well as with previous pregnancy losses [59] and previous elective terminations [37].

Infant Sex

Some data suggest that infant sex is associated with gastroschisis risk, although evidence for this is mixed. Several studies suggest that males are more likely than females to have gastroschisis [6, 7, 10, 11, 14, 18, 20, 35, 37], while one analysis found females have the greater risk [33]. However, many recent studies have found no association between the rates of gastroschisis and infant sex [1, 22, 24, 26, 36, 39].

FACTORS IN LIFESTYLE OR ENVIRONMENT

Maternal Health

Some investigations have found a significant association between gastroschisis and prior history of gynecological infections, such as sexually transmitted infections and urinary tract infections [23, 24].

Studies have suggested that inadequacies in the mother’s diet or lack of nutrition may increase risk for gastroschisis [59, 61]. Other examinations have found similar associations between supplement use and risk for gastroschisis. Folic acid use has been associated with a decreased risk of gastroschisis [42-44]. Lack of prenatal vitamin use has been associated with an increased risk of gastroschisis [45, 46, 62]. In contrast to several other types of birth defects, a strong link between low maternal pre-pregnancy body mass index and gastroschisis has been identified [24, 43, 45, 59]. Further, obesity or overweight status prior to pregnancy seems to have a protective effect against gastroschisis [63, 64]. Gastroschisis risk and intake of fat and cholesterol have been explored but only a weak association or a lack of association has been found [43, 45].

Smoking

Women who smoke during pregnancy may be more likely to have an infant with gastroschisis [22-24, 26, 35, 37, 39-44, 46, 49, 65], although not all investigations found this effect [50, 56].

Drugs and Medication

Maternal consumption of caffeinated or decaffeinated coffee has not been found to increase gastroschisis risk [50], nor has caffeine intake [66]. Maternal alcohol use has been linked to higher rates of gastroschisis [37, 39, 42, 43, 50], however at least one study contradicts these findings [24].

Recreational drug use (cocaine, crack, ecstasy, amphetamine, marijuana, or LSD use) has also been associated with an increased risk for gastroschisis [23, 37, 43, 44, 67], but other studies did not observe this association [25, 39, 56]. Overall, results for the association between various recreational drugs and gastroschisis risk have been mixed.

The link between maternal cocaine use and increased gastroschisis risk is of particular interest because cocaine is a vasoconstrictor, and there is some evidence thatgastroschisis is a vascular disruption defect [38, 42, 68, 69]. This hypothesis is supportedby research that found increased rates of gastroschisis among infants born to mothers who had used vasoactive medications [23, 44-46, 51, 59, 70-72] including:

salicylates (aspirin)

pseudoephedrine

phenylpropanolamine

Some evidence contradicts this hypothesis [39, 42]. One study found no link between decongestant or bronchodilator use and gastroschisis risk [42], but another did find increased risk with bronchodilator use [44].

A recent study found an association between maternal opiod use (in medications such as codeine, hydrocodone, and oxycodone) and risk of gastroschisis [73].

There may be a connection between the use of over-the-counter (OTC) medications, including pseudoephedrine, and the prevalence of gastroschisis [72, 74]. Although these findings are not entirely consistent [39, 58, 70, 72]. Drugs (commonly used in OTC cough, cold, and allergy medications) that seem to confer higher risk include:

One analysis found acetaminophen to have a slight protective effect when used to treat fever or infection [58].

In one investigation, antibiotics, anti-nauseants, sulfonamides, and oral contraceptives were not linked to gastroschisis risk [70]. Another examination also failed to find an association between antibiotic use and risk of gastroschisis [24]. Oral contraceptive use has been linked to an increased risk for gastroschisis in some studies [42, 65].

Other

Some other possible risk factors for gastroschisis have been explored. One investigation found higher risk with spring conception season and residing less than fifty kilometers from a site of high Atrazine concentration, a commonly used herbicide [60]. In another recent study, an association was found among women relying on public water systems which draw from surface water sources, but no association was found between gastroschisis risk and prenatal exposure to upstream textile mill pollutants [75]. One study found an association between gastroschisis risk and maternal exposure to solvents and colorants, and periconceptional x-ray exposure [70].

REFERENCES

1. Salihu HM, Pierre-Louis BJ, Druschel CM, Kirby RS: Omphalocele and gastroschisis in the State of New York, 1992-1999. Birth Defects Research Part A, Clinical And Molecular Teratology 2003, 67(9):630-636.

14. Baird PA, MacDonald EC: An epidemiologic study of congenital malformations of the anterior abdominal wall in more than half a million consecutive live births. American Journal Of Human Genetics 1981, 33(3):470-478.

20. Hemminki K, Saloniemi I, Kyyrönen P, Kekomäki M: Gastroschisis and omphalocele in Finland in the 1970s: prevalence at birth and its correlates. Journal Of Epidemiology And Community Health 1982, 36(4):289-293.

42. Werler MM, Mitchell AA, Moore CA, Honein MA: Is there epidemiologic evidence to support vascular disruption as a pathogenesis of gastroschisis?American Journal Of Medical Genetics Part A 2009, 149A(7):1399-1406.

74. Gastroschisis and pseudoephedrine during pregnancy. Prescrire International 2004, 13(72):141-143.

75. Root ED, Emch ME: Tracing drinking water to its source: An ecological study of the relationship between textile mills and gastroschisis in North Carolina. Health & Place 2010, 16(5):794-802.

Please Note: The primary purpose of this report is to provide background necessary for epidemiologic research. It summarizes literature about risk factors associated with this defect. The strengths and limitations of each reference were not critically examined prior to inclusion in this report. Consumers and professionals using this information are advised to consult the references given for more in-depth information. This report is for information purposes only and is not intended to diagnose, cure, mitigate, treat, or prevent disease or other conditions and is not intended to provide a determination or assessment of the state of health. Individuals affected by this condition should consult their physician and when appropriate, seek genetic counseling.